Field of the Invention
The present invention relates to systems and methods for calibrating thermal sensors. More particularly, aspects of the present invention relate to systems and methods for using a single slug comprising one or more calibrators or multiple slugs comprising one or more calibrators to calculate a relationship between temperature and an electrical characteristic of the thermal sensor for use in connection with calibrating thermal sensors.
Description of the Background
Devices for performing chemical, biological, or other reactions (e.g., a microfluidic device for performing polymerase chain reaction (PCR) amplification of DNA molecules, or a microfluidic molecular diagnostic platform that performs PCR on a patient sample and then uses the PCR product for genotyping by performing a high resolution melt analysis) often feature one or more thermal control elements that are used to subject reactants to a desired thermal profile. A description of PCR amplification, and an example of one possible microfluidic device including thermal control elements for PCR amplification and thermal melt analysis, are provided in U.S. patent application Ser. No. 12/165,043, which is hereby incorporated herein by reference. A description of the field trial unit (FTU) referred to in the present application can be found in U.S. patent application Ser. No. 13/223,290, which is hereby incorporated herein by reference.
In many applications of such microfluidic devices (e.g., PCR and/or thermal melt analysis), the thermal control elements of those devices must be precisely calibrated. That is, the correspondence between the temperature of the thermal control element and an electrical characteristic of the thermal control element must be precisely determined. For example, in the case of a resistance temperature detector, the correspondence between temperature and resistance must be precisely determined. Additional types of thermal control elements can include platinum resistive heaters, thermistors, diode temperature sensors, thermocouples, or any other suitable temperature measuring devices. Additional electrical characteristics of thermal control elements that correspond to temperature can include capacitance or inductance of an element, frequency, pulse width, or amplitude of a signal, or other sensor characteristics known in the art. Methods of calibrating thermal control elements often include generating a lookup table or a series of coefficients that define a calibration equation, i.e., a lookup table or an equation relating the temperature of the thermal control element with the electrical characteristic.
Calibration can be performed by sending the device to a third party laboratory for taking accurate measurements and generating the lookup table or series of coefficients; however, this procedure is generally expensive and time consuming. Furthermore, for many devices (e.g., many common microfluidic devices) there may be many thermal control elements (e.g. dozens or even hundreds of heaters and sensors), each of which requires its own precise calibration, making third-party calibration impractical.
The present microfluidic system utilizes a microfluidic chip referred to herein as a U chip, which is contained with a cartridge. Throughout the present invention, U chip and microfluidic chip will be used interchangeably. Several variables can cause fluid temperature variance within U chip microfluidic channels. Heater calibration is utilized to correct for these combination of factors to provide a more accurate result with functional testing by melting amplicon, measuring the melting temperature (Tm), and then adjusting software settings for how power is delivered to the heaters. The heater calibration process itself introduces some error into temperature correction due to calibrator formulation variation and melting curve smoothing/calculations to match the reference melting curve for heater parameter adjustment.
Accordingly, what is desired is robust calibration of thermal sensors that can be accurate, reduce downtime and maintain high throughput.